Regulator levels play an important role in the emergence and progression of leukemic clones. Microenvironmental influences within bone marrow are critical for hematopoietic stem cell proliferation and differentiation, and depend upon normal maturation of monocytic and granulocytic cells. Thus a functionally normal myeloid compartment is a requisite for normal hematopoietic differentiation. Soft agar culture techniques which detect committed granulocyte-macrophage progenitor cells (CFU-GM) in bone marrow will be utilized to assess the ability of patient cells to respond to three specific compounds which ply a definitive role in the in vitro regulation of myeloid stem cell proliferation: colony stimulating factors (CSF), Prostaglandin E (PGE) and Lactoferrin (LF). In addition, the ability of each patient's mature myeloid cells (polymorphonuclear neutrophils (PMN) and monocytes and macrophages) to mediate normal stem cell regulation will be investigated by quantitating monocyte-macrophage CSF and PGE production, and the ability of LF to modulate the synthesis/release of these products from monocytoid cells. Biophysical and immunological cell separatory procedures will be employed to evaluate the contribution of cell population heterogeneity to the observed results and as a means to further define responding cell populations. Site(s), mechanism(s) of action and physiological significance of specific feedback regulation in the development and progression of acute and chronic myeloid leukemias and myelodysplastic diseases will be determined.